The present invention relates to bio-separation, and more particularly to an interface mechanism in a bio-separation instrument, which supports the use and functions of a multi-channel capillary cartridge, in particular a multi-channel cartridge having multi-separation columns with integrated reagent reservoir and excitation radiation and detection optics.
Bioanalysis, such as DNA analysis, is rapidly making the transition from a purely scientific quest for accuracy to a routine procedure with increased, proven dependability. Medical researchers, pharmacologists, and forensic investigators all use DNA analysis in the pursuit of their tasks. Yet due to the complexity of the equipment that detects and measures DNA samples and the difficulty in preparing the samples, the existing DNA analysis procedures are often time-consuming and expensive. It is therefore desirable to reduce the size, number of parts, and cost of equipment, to ease sample handling during the process, and in general, to have a simplified, low cost, high sensitivity detector.
One type of DNA analysis instrument separates DNA molecules by relying on electrophoresis. Electrophoresis techniques could be used to separate fragments of DNA for genotyping applications, including human identity testing, expression analysis, pathogen detection, mutation detection, and pharmacogenetics studies. The term electrophoresis refers to the movement of a charged molecule under the influence of an electric field. Electrophoresis can be used to separate molecules that have equivalent charge-to-mass ratios but different masses. DNA fragments are one example of such molecules.
There are a variety of commercially available instruments applying electrophoresis to analyze DNA samples. One such type is a capillary electrophoresis (CE) instrument. By applying electrophoresis in a fused silica capillary column carrying a buffer solution, the sample size requirement is significantly smaller and the speed of separation and resolution can be increased multiple times compared to the slab gel-electrophoresis method. These DNA fragments in CE are often detected by directing light through the capillary wall, at the components separating from the sample that has been tagged with a fluorescence material, and detecting the fluorescence emissions induced by the incident light. The intensities of the emission are representative of the concentration, amount and/or size of the components of the sample. In the past, Laser-induced fluorescence (LIF) detection methods had been developed for CE instruments. Fluorescence detection is often the detection method of choice in the fields of genomics and proteomics because of its outstanding sensitivity compared to other detection methods.
Some of the challenges in designing CE-based instruments relate to the support of the capillaries and alignment of the capillaries to support elements (e.g., excitation and detection optics). Biocal Technology, Inc. developed a CE-based instrument and a multi-channel cartridge for use therein, which comprises multi-separation columns with integrated reagent reservoir and excitation radiation and detection optics. (The Biocal cartridge and system are described in U.S. patent application Ser. No. 10/059,993 and U.S. patent application Ser. No. 10/060,052, which had been incorporated by reference herein). The cartridge is designed to be supported by the instrument, with all essential cartridge elements aligned and coupled to support elements in the instrument. It is desirable to provide a reliable and secure interfacing mechanism in the instrument to make such coupling to the cartridge.